Differential Effects of Directional Cyclic Stretching on the Functionalities of Engineered Cardiac Tissues

Cardiac tissue engineering aims to regenerate functional cardiac tissues through recapitulating the native microenvironmental cues, where cardiomyocytes are highly oriented and rhythmically contract along their long-axis direction in the native myocardium. In addition, the different oriented layers of the left ventricle lead to a dynamic biaxial stretching on cardiomyocytes, which makes the mechanical microenvironment in the myocardium much more complex. Thus, it is important to investigate the effect of dynamic mechanical stimulation along different directions to preoriented cardiomyocytes on the functionalities of engineered cardiac tissues. In this study, we regenerate oriented cardiac tissues using electrospun silk fibroin scaffolds, followed by applying the dynamic mechanical stimulation parallel or perpendicular to the cell orientation. The design and utilization of nanofibrous scaffolds combining the aligned topography and random substrate ensure the realization of dynamic mechanical stimulation with a homogeneous strain along both directions. The results reveal that the parallel mechanical stretching promotes the alignment of cardiomyocytes and the formation of sarcomeres and gap junctions, while the perpendicular stimulation interferes with the cell alignment and gap junction formation. This study would provide guidance for promoting the functionalities of regenerated cardiac tissues through directional dynamic mechanical stimulation.